Bacterial biofilms cause significant infections in the medical field. Antibiotics commonly used to treat these infections often do not achieve complete bacterial eradication. New approaches to eliminate biofilms have focused on dispersion compounds to entice the bacteria to actively escape or disperse from the biofilm, where the bacteria may become more susceptible to antibiotics.
Current researches have identified the genes that may be specifically involved in increased resistance of biofilm cells, where there has been isolated several mutants of uropathogenic Escherichia coli, and Staphylococcus aureus and which form “normal” biofilms, but which do not possess increased resistance. The persistence of, for example, staphylococcal infections related to foreign bodies is due to biofilm formation. Likewise, chronic Pseudomonas aeruginosa lung infection in cystic fibrosis patients is caused by biofilm-growing mucoid strains. Furthermore, biofilm growth is associated with an increased level of mutations as well as with quorum-sensing-regulated mechanisms.
Characteristically, gradients of nutrients and oxygen exist from the top to the bottom of biofilms and these gradients are associated with decreased bacterial metabolic activity and increased doubling times of the bacterial cells; it is these more or less dormant cells that are responsible for some of the tolerance to antibiotics. Biofilms may be prevented by early aggressive antibiotic prophylaxis or therapy and may be treated by chronic suppressive therapy.
Moreover, a term that may be commonly used for chronic diseases as consequence of bacterial biofilms is bacterial chemotaxis. Specifically, chemotaxis may be described as the directed cell locomotion in concentration gradients of soluble extracellular agents. Substances that induce a chemotactic response (chemotactic factors) are known also under the general name of cytotaxin, chemotaxin, or chemo-attractants. Additionally, cells showing positive chemotaxis move towards areas with higher concentrations of chemotactic agents, while those showing negative chemotaxis moves away from these areas.
Numerous active pharmaceutical ingredients (APIs) such as antibiotics in combination with chemotactic agents have been studied in order to produce a pharmaceutical composition that could be effective in disrupting bacterial biofilms. However, there is no specific research that could provide a suitable dosage or concentration of antibiotics, chemotactic agent, or any other chemical agent to kill or eradicate the biofilms in different sites of human body.
There is therefore a need for pharmaceutical compositions that may include chemotactic agents combined with APIs, such as antibiotics, and other ingredients that could be effective for disrupting bacterial biofilms or microbial colonies. Therefore, various dosage forms of the pharmaceutical composition that include chemotactic agents may be used for treating some chronic diseases.